The present invention relates to apparatus, systems, and methods utilizing cryogenic cooling in an angioplasty balloon catheter for treatment of arterial stenosis and prevention of restenosis. More particularly, the present invention relates to an angioplasty balloon catheter utilizing expansion of compressed gas to effect Joule-Thomson cooling of an angioplasty balloon, and optionally further incorporating external temperature sensors utilizable to identify a locus for treatment of arterial stenosis. The present invention further relates to angioplasty treatment systems incorporating such a catheter, and to cryogenic angioplasty methods for treating arterial stenosis and discouraging restenosis.
It is a well-known problem of angioplastic surgery that blood vessels having been subjected to angioplastic treatment have a marked tendency to undergo restenosis. Blood vessels having displayed improved vascular flow as result of an angioplasty intervention are often observed to suffer a subsequent re-narrowing of the vessel, again impeding vascular flow, in the weeks and months following the angioplasty intervention. Such restenosis is currently understood to be a reaction of vascular tissues to the angioplastic procedure, or to the ongoing endovascular insult.
Cooling of the site during or immediately following angioplasty has been found to impede or prevent restenosis. A number of patents have been issued relating to devices for cryogenic cooling of tissues during or after angioplasty, and to angioplasty methods using cooling devices.
U.S. Pat. No. 5,868,735 to Daniel M. Lafontaine, and U.S. Pat. No. 4,290,686 also to Lafontaine, both refer to cryogenic cooling of an angioplasty apparatus, as does U.S. Patent Application 20020032438 by Lafontaine.
Lafontaine teaches a method whereby a balloon catheter is advanced to a target site, the balloon is inflated, and coolant is delivered into the inflated balloon to freeze a portion of a lesion adjacent to the balloon, to kill cells within the lesion.
It is, however, a limitation of the above-mentioned Lafontaine patents and patent application that the implementations described are limited to cryogenic cooling by evaporation of a liquid.
As is well known, evaporation from a liquid cools that liquid. If a liquid, such as for example liquid nitrogen, is maintained under pressure to prevent boiling, and then is passed into an area where it is free to expand, released pressure allows boiling or rapid evaporation of the liquid, cooling both the liquid and the resultant gas.
Cooling by evaporation is described by Lafontaine as the method of choice for cryogenic cooling of a cryoplasty balloon catheter to effect cooling of tissues at an angioplasty site. We note that although claim 13 of U.S. Pat. No. 6,290,696 op. cit. is couched in general terms, in that Lafontaine refers to delivering coolant into the balloon and allowing the coolant to undergo a phase change within the balloon, the phase change actually described within Lafontaine's disclosure is a phase change from liquid to gas, that is, cooling by evaporation.
U.S. patent application Ser. No. 20020010460, submitted by James Joye et. al. similarly refers to a cryosurgery probe usable to perform angioplasty, which probe enables cryogenic cooling of tissues at an angioplasty site. Joye refers to an apparatus in which a single balloon may function for both cryogenic cooling and for dilation.
Joye's application similarly contemplates cooling by evaporation. Throughout his disclosure, Joye presents and discusses cooling by evaporation from supplied cooling liquids or liquid/gas mixtures such as carbon dioxide (CO.sub.2), nitrous oxide (N.sub.2O), liquid nitrogen (N.sub.2), a fluorocarbon such as AZ-50.TM. (sold by Genetron of Morristown, N.J.), or the like. Similar systems are presented U.S. Pat. No. 6,355,029 to Joye et. al. and in U.S. Pat. No. 5,971,979, also to Joye et. al.
It is to be noted that in each of the above-mentioned documents Joye refers in passing to the possibility of use of a Joule-Thomson orifice in the delivery of a cryogenic cooling fluid into an angioplasty balloon, yet in each of the documents, all of the implementation details refer to delivery of a liquid rather than a gas into a balloon or other volume to be cryogenically cooled. In this sense, the embodiments described in detail by Joye are similar to those described by Lafontaine in the patents cited hereinabove, in that evaporation of a liquid, a phase transition from a liquid to a gaseous state, is the cooling mechanism described. Thus, for example, Joye states in one context “the cryogenic fluid will flow through the tube 22 as a liquid at an elevated pressure and (thus inhibiting flow restrictive film boiling) will expand across the orifice 23 to a gaseous state at a lower pressure within the balloon.” And similarly: “The methods of the present invention may be performed with cryosurgical catheters comprising a catheter body having a proximal end, a distal end, and a primary lumen therethrough. The primary lumen terminates in a Joule-Thomson orifice at or near its distal end, and a balloon is disposed over the orifice on the catheter body to contain a cryogenic fluid delivered through the primary lumen. Suitable cryogenic fluids will be non-toxic and include liquid nitrogen, liquid nitrous oxide, liquid carbon dioxide, and the like. By delivering the cryogenic fluid through the catheter body, the balloon can be expanded and cooled in order to effect treatments according to the present invention.”
Thus, it is to be noted that although Joye employs the term “Joule-Thomson orifice”, he uses it to describe a system wherein a pressurized liquid passes into a region where it is enabled to evaporate, thereby to effect cooling. This is to be contrasted to the embodiments to be described hereinbelow, wherein the cryogenic fluid delivered to an expandable balloon is a pressurized gas, not a liquid nor a liquid/gas mixture, and wherein expansion of a pressurized gas, and not evaporation of a liquid, is the cooling mechanism. Although the two methods are similar in that both allow for expansion of a compressed fluid, they are also, in a sense, almost opposite, in that the phase change initiated by delivery of a pressurized liquid into the balloon volume is a phase change from liquid to gas, whereas in a true Joule-Thomson delivery system a gas is allowed to expand, and by expansion to cool, and the result of that cooling process may even be, in some cases, a phase transition in the opposite direction, whereby the expanded gas is cooled to such an extent that a portion of the expanded gas actually condenses back into liquid phase.
Various other patents similarly refer to cooling by evaporation as a method of cryogenic cooling of an angioplasty balloon catheter. U.S. patent application Ser. No. 20020045892 by Hans W. Kramer is an additional example of a system utilizing evaporation of a liquid such as perfluorocarbon to achieve cryogenic cooling in a balloon catheter. U.S. Pat. No. 5,147,355 to Peter Friedman is yet another example of a system utilizing evaporation of a liquid to achieve cryogenic cooling.
Cooling by evaporation, however, presents a variety of disadvantages.
Cooling by evaporation is relatively slow when compared, for example, to true Joule-Thomson cooling, that is, when cooling by evaporation is compared to cooling by allowing rapid expansion of a compressed gas.
Further, evaporative cooling is not amenable to exact control of the cooling process, because evaporation is not instantaneous. Introducing into an angioplasty balloon a liquid which cools by evaporation inevitably introduces an intrinsic lag in any possible control of the cooling process, because halting the supply of cooling fluid does not immediately halt cooling. Liquid previously introduced into a balloon and not yet evaporated will continue to cool even after supply of additional cooling liquid has been halted. In the surgical context of angioplasty interventions, where treatment typically necessitates blocking of arteries during a procedure, speed of operation and fine control of temperatures are of great importance.
Thus, there is a widely felt need for, and it would be highly advantageous to have, an apparatus and method of cooling an angioplasty balloon which provide for rapid cooling and optional rapid heating of an angioplasty balloon, and which enable accurate, rapid, and exact control of temperatures within the angioplasty balloon and/or in the treated body tissues.
Joye's discussion of uses of his invention, in the documents cited above, points up several additional problematic aspects of cryogenic cooling by evaporation. Joye describes the difficulty of achieving an optimal cooling temperature at a target region, and further describes the difficulty of achieving an even cooling distribution throughout a target region.
With respect to maintenance of a desired temperature within the cooling apparatus, Joye points out that it is in many cases desirable to invoke apoptosis and/or programmed cell death so as to inhibit hyperplasia and/or neoplasia of a blood vessel related to angioplasty, stenting, rotational or directional artherectomy, or the like, and he further points out that in order to invole apoptosis (rather than simply destroying tissues by radical deep freezing) it will often be desirable to provide more moderate cryogenic treatment temperatures than those automatically provided by an uncontrolled evaporation process. Joye does not, however, provide a method of achieving exact control of cooling within the target regions. Indeed, he points out that cooling is generally enhanced by minimizing pressure within the angioplasty balloon. This link, between pressure of gas within an inflated balloon and the amount of cooling of that balloon, is one of the disadvantages of using an evaporation process to achieve cryogenic cooling of an angioplasty balloon.
Thus, there is a widely recognized need for, and it would be highly advantageous to have, an apparatus and method of cryogenic cooling in an angioplasty balloon catheter which provides for exact control of temperature within a balloon in a manner relatively independent of the dilation pressure maintained in that balloon.
With respect to the well-known difficulty of achieving an even cooling distribution throughout a target region, Joye discusses the fact that evaporative cooling tends to cool an apparatus unevenly, parts of the apparatus adjacent to a lumen through which cooling fluid is supplied being significantly colder than more distant parts of the apparatus. In an attempt to deal with the problem, Joye proposes a method distribution of a cryogenic liquid from a supply lumen into a cryogenic balloon, utilizing a diffuser that causes the cooling fluid to be distributed both radially and axially. The contemplated diffuser comprises a tubular structure with radially oriented openings. Joye points out that as the openings are radially oriented, the diffuser will direct the cooling fluid roughly perpendicularly toward the wall of the cryogenic balloon, thereby encouraging even heat transfer between the cooling vapor and balloon wall. Joye teaches that distribution of ports circumferentially and axially along the balloon provides a substantially uniform cooling over a significant portion of (often over the majority of) the surface of the balloon. A similar system is also described by Joye in U.S. Pat. No. 6,355,029. We note however that according to Joye's own description, the desired uniformity is not expected to extend over the entire surface of the balloon, and in many cases will not extend even to the majority of the balloon surface.
Thus, there is a widely recognized need for, and it would be highly advantageous to have, apparatus and method of cryogenic cooling of the balloon of an angioplasty balloon catheter, which method and apparatus provide for accurate control of temperature of the balloon during cooling, and further provide a highly evenly distribution of cold throughout that balloon catheter.
With respect to another aspect of cryogenic balloon angioplasty, U.S. patent application Ser. No. 20020045894 by James Joye et. al. presents an additional system for cryogenic cooling by evaporation, this system comprising a double balloon catheter, a first balloon being inflated by a pressurized gas, and a second balloon containing the first balloon, with a vacuum between the two. In U.S. patent application Ser. No. 20020045894 Joye presents a safety interlock system, whereby a rise in pressure in the outer balloon is interpreted to signal a leak in the inner balloon, and detection of such a rise in pressure causes his system to cut off supply of pressurized fluid to the inner balloon, thereby avoiding an irruption of pressurized fluid into the tissues of a patient undergoing a surgical intervention. We note, however, a disadvantage of the described safety interlock system, in that it is designed to detect such a leak only after a significant rise in pressure has occurred within the outer balloon.
Thus, there is a widely recognized need for, and it would be highly advantageous to have, a system for detecting a leak in such a balloon angioplasty system, which detection is highly sensitive to even very small leaks in an inner angioplasty balloon, thereby enabling to immediately cease supply of input fluids, and to undertake other or additional corrective measures, as soon as such a very small leak is detected, and without necessitating waiting for a leak large enough to significantly raise pressure in an outer balloon volume.
Referring now to other aspects of prior art, it is noted that one of the basic problems inherent in angioplasty and similar surgical interventions is the need to effect correct placement of an angioplasty balloon catheter prior to performance of angioplasty. There is thus a widely recognized need for, and it would be highly advantageous to have, apparatus and method enabling accurate placement of an angioplasty balloon catheter based information garnered at a potential intervention site, by an angioplasty balloon catheter, in real time.